Irritable bowel syndrome (IBS) is a biopsychosocial disorder. 5-Hydroxytryptamine (5-HT) plays a crucial role in the control of gastrointestinal motility, sensation, and secretion. This study investigated changes in platelet-depleted plasma 5-HT and their correlation with psychopathology in IBS patients and healthy subjects.

This study involved 21 subjects with IBS and 13 healthy subjects. Fasting and 1-hr postprandial plasma 5-HT concentrations were measured. The SCL-90R symptom checklist was used for the assessment of current psychological symptoms.

Fasting and postprandial plasma 5-HT concentrations were significantly higher in IBS patients (15.11+/-13.51 ng/mL and 16.31+/-14.21 ng/mL, respectively) than in healthy subjects (5.55+/-4.14 ng/mL and 6.25+/-4.82 ng/mL, respectively; p<0.05). There were no significant changes between fasting and 1-hr postprandial 5-HT concentration in IBS subtypes and healthy subjects. Scores on all SCL-90R subscales except for the interpersonal-sensitivity subscale were significantly higher in IBS patients than in healthy subjects. No correlation was found between SCL-90R items and platelet-depleted plasma 5-HT concentration.

5-HT might play a critical role in IBS, and psychopathological factors are correlated with IBS.

Gilbert's syndrome is a common inherited disorder, in which genetic defects in uridine diphosphate-glucuronosyltransferase 1A1 lead to deficient glucuronidation of bilirubin and hence hyperbilirubinaemia. Although usually considered asymptomatic, Gilbert's syndrome can be associated with gastrointestinal and psychiatric symptoms unexplained by the metabolic defect. Genetic polymorphism of a closely related enzyme, uridine diphosphate-glucuronosyltransferase 1A6, results in altered metabolism and elimination of serotonin. On the basis of a case of hyperserotoninaemia in the absence of a detectable carcinoid tumour in a patient with Gilbert's syndrome, who presented with a history of night sweats, flushing, abdominal discomfort and intermittent diarrhoea, we propose that in a subgroup of Gilbert's syndrome patients, homozygocity for dual uridine diphosphate-glucuronosyltransferase 1A1 and uridine diphosphate-glucuronosyltransferase 1A6 polymorphisms may lead to combined hyperbilirubinaemia and hyperserotoninaemia. The latter may account for symptoms experienced by patients with Gilbert's syndrome hitherto considered unrelated to, or unexplainable by, the known defect in bilirubin metabolism.

The possibility that 5-hydroxytryptamine (5-HT) acts as a key sensitising agent in the aetiology of irritable bowel syndrome (IBS) is reviewed. The strategic locations of 5-HT and its receptors are described, the most dominant being the 5-HT3 and 5-HT4 type. 5-HT, acting mostly at 5-HT3 or 5-HT3-like receptors, enhances the sensitivity of visceral neurones projecting between the gut and the central nervous systems. 5-HT, acting at 5-HT4 receptors promotes the sensitivity of enteric neurones that react to luminal stimuli. 5-HT4 and 5-HT3 receptors also mediate, respectively, sensitising and physiological actions of 5-HT on gastro-intestinal motor and secretory functions. This distribution implies that some 5-HT3 receptor antagonists might reduce certain symptoms of IBS, such as pain, by reducing the reactivity of the visceral afferent neurones linking the gut with the brain and spinal cord. However, such antagonists are not likely to find widespread clinical acceptance because they can also affect normal lower bowel function and promote constipation. 5-HT4 receptor antagonists, by contrast, reduce 5-HT-induced enteric nerve hypersensitivity without notably affecting the function of the normal bowel. Accordingly, these agents may reduce the symptoms of IBS directly, by reducing the incidence of defecation and diarrhoea and indirectly, by reducing both 'rebound' constipation and the post-prandial discomfort and pain associated with gastrointestinal hyper-reactivity.

Buspirone stimulates central 5-hydroxytryptamine (5HT) receptors and brings about the release of prolactin, and there is evidence to suggest that the extent of prolactin release after a challenge with buspirone is an indicator of the sensitivity of central 5HT receptors. Seventeen patients with a diagnosis of non-ulcer dyspepsia, eight normal healthy volunteers, and six patients with peptic ulcer disease were each given a challenge test of 60 mg buspirone orally, and prolactin release over a 3-h period was monitored. The mean prolactin response was significantly greater in patients with non-ulcer dyspepsia than in healthy controls and peptic ulcer disease patients. The results suggest that central 5HT receptors may be supersensitive in non-ulcer dyspepsia.

Cholera enterotoxin introduced into the duodenum of young rabbits causes severe degranulation of the enterochromaffin (EC) cells as revealed by electron microscopy. In the mucosal epithelium fixed mainly 1 hr after toxin administration, many of the basal granules of the EC cells are swollen up and open to the basal and lateral cell surface. The EC cells of the rabbit, as it is the rule for intestinal endocrine cells in mammals, are open to the lumen with an apical process covered by microvilli. A hypothesis is proposed that cholera toxin stimulates this apical receptor of the EC cells and that the aminic (serotonin) and polypeptide (motilin?) products of the cells released by the stimulus may mediate the diarrhoeagenic action of cholera enterotoxin.